#18-019

Progress

Date Full Report Received

03/29/2020

Date Abstract Report Received

03/29/2020

Investigation

Institution:
Primary Investigator:

Funded By

Virulent swine influenza A virus (SwIAV) infection causes acute febrile respiratory disease in pigs of all ages, and it is a serious economic burden to the US pork industry. The commercial inactivated multivalent swine influenza virus vaccine delivered by intramuscular injection provides variable degrees of protection against field virus outbreaks. Delivery of vaccine by injection elicits mainly systemic immunity with poor mucosal immunity, while intranasal vaccines could induce both mucosal and systemic immunity. Our goal was to develop a potent intranasal inactivated/subunit swine flu vaccine which provides the increased breadth of immunity. Stable and biodegradable nanoparticles delivered vaccine antigens are readily taken up by immune cells and induce heightened immunity compared to non-particulate soluble antigens in the vaccine. In an initial in vivo study, we combined inactivated SwIAV antigens entrapped in poly(lactic-co-glycolic acid) nanoparticle with surface coated SwIAV antigens on sweet corn-based Nano-11 particles to augment cross-reactive T and B cell responses including mucosal IgA response for achieving enhanced cross-protection and reducing the SwIAV load in the airways of pigs, but our results were inferior to commercial SwIAV vaccinated animals. In our subsequent studies, inactivated SwIAV antigens and adjuvant poly(I:C) were adsorbed on corn-derived Nano-11 nanoparticle and evaluated its efficacy in intranasally vaccinated nursery pigs which were positive or negative for influenza maternal antibodies. Our study results indicated that the candidate nanoparticle flu vaccine augmented vaccine virus specific and cross-reactive antibodies in the respiratory tract better than the commercial swine flu vaccine in both antibody free and positive pigs at the time of vaccination. In addition, compared to in influenza antibody free pigs, in antibody positive pigs the corn nanoparticle-based flu vaccine delivered with poly(I:C) elicited heightened cross-reactive cell mediated immune response compared to commercial vaccine. The data of lung pathology and viral load in the airways were comparable in both the corn nanoparticle and commercial flu vaccine received virus challenged pigs. Because the HA gene identify data between the vaccine H1N1 SwIAV present in commercial flu vaccine and challenge H1N1 virus was greater than 95%, compared to 77% HA identify between our candidate corn nanoparticle vaccine H1N2 virus with the challenge H1N1 virus. Therefore, our study data suggested that intranasal corn-based nanoparticle flu vaccine is superior in enhancing the cross-protective immunity compared to a commercial injectable vaccine irrespective of the maternal antibody status in pigs.

1. Objectives:
Objective of our study was to analyze the cross-protective efficacy of sweet corn nanoparticle-based swine influenza A virus vaccine in nursery pigs positive and negative for maternal antibodies.

2. How research was conducted:
Inactivated swine influenza A virus (SwIAV)-H1N2 was used in experimental inactivated virus vaccine preparation. The virus used for challenge infection was a virulent and zoonotic H1N1-OH7 SwIAV. Both inactivated virus (SwIAV) and conserved peptides and poly(I:C) were adsorbed on corn nanoparticles. The FluSure XP® commercial inactivated multivalent SwIAV vaccine was purchased from Zoetis (MI, USA). Experimental three-week-old influenza virus maternal antibody positive and five-week-old negative nursery pigs were vaccinated intranasal, and the commercial vaccine by intramuscular route as per manufacturer’s instructions. Immunological analyses were performed to determine antibody and cell mediated responses. Statistical analyses of immune responses and virus shedding data were carried out. A p<0.05 was considered statistically significant. Data were presented as the mean ± SEM of four to six pigs per group.

3. Research findings:
The commercial inactivated influenza virus vaccine is a multivalent virus formulation meant for intramuscular route of delivery in pigs. In vaccinated pigs, an increased specific IgG antibody response in serum and lung parenchyma was detected in commercial vaccine administered animals. Intranasal vaccination elicits mucosal secretory IgA antibody response in the airways which is required for cross-protection against influenza. Our corn nanoparticle-based inactivated monovalent SwIAV vaccine delivered with poly(I:C) augmented both specific and cross-reactive IgA antibodies in both the upper and lower respiratory tract of pigs which were positive or negative for maternal antibody. While the IgG response in commercial vaccine injected pigs was downregulated in maternal antibody positive compared to maternal antibody negative pigs. The cross-reactive cell mediated immune response in corn nanoparticle-based swine flu vaccine delivered with poly(I:C) was upregulated substantially compared to commercial vaccine in maternal antibody positive pigs.

4. What these findings mean to the industry:
Sweet corn-based nanoparticles (<100 nm diameter) adsorbed killed SwIAV along with an adjuvant poly(I:C) delivered intranasal has the ability to induce homologous, heterologous and heterosubtypic virus specific antibody and cell-mediated responses in the airways and systemically both in the presence and absence of maternal antibody at the time of vaccination. This induced response can provide cross-protective immunity. Therefore, intranasal delivery of inactivated SwIAV particulate vaccine with a suitable adjuvant may be a better alternative to commercial injectable vaccine both in the presence or absence of maternal antibodies. While maternal antibodies in nursery pigs interferes with the specific serum IgG production by injectable commercial SwIAV vaccine.

5. Include your contact information.
Dr. Renukaradhya J. Gourapura, DVM, MS, PhD
Professor
Food Animal Health Research Program, OARDC
The Ohio State University
1680 Madison Ave, Wooster, OH 44691
Ph: (330) 263-3748; Fax: 330-263-3677
gourapura.1@osu.edu